[unreadable] Preliminary studies utilizing optical coherence tomography (OCT) have demonstrated that this high-resolution imaging modality can facilitate the accurate diagnosis of a variety of diseases, including coronary atherosclerosis and cancer. Presently, the image acquisition rate of state-of-the-art OCT technology is limited to a few frames per second and therefore micro-structural diagnostic information can only be obtained at discrete locations. The potential diagnostic applications having the highest impact, however, require screening or surveillance of large tissue volumes. Since the current technology commonly operates at its theoretical limit of detection sensitivity, dramatic improvements in imaging speed can only be obtained through a fundamental technological paradigm shift. [unreadable] We propose to develop a new optical tomographic imaging method based on optical frequency domain reflectometry. Our preliminary studies show that optical frequency-domain imaging (OFDI) technology can offer several-hundred-fold higher sensitivity and more than ten-fold faster imaging speed than the existing OCT technology. The objective of this research is to develop and validate OFDI for high-speed, high-sensitivity, in vivo clinical imaging. The design of the proposed technology is tailored to two high-impact clinical goals: comprehensive surveillance for esophageal neoplasia in patients with Barrett's esophagus and characterization of vulnerable coronary plaques responsible for acute myocardial infarction. Two clinical pilot studies, using technology developed in this work, will be conducted to test system performance relevant to achieving these goals. [unreadable] [unreadable]